An efficient synthesis of ofloxacin and levofloxacin from 3,4- difluoroaniline

Heterocycles

Volumn 51, Issue 7, 1999, Pages 1563-1572

  Adrio, Javier ^a   Carretero, Juan C ^a   García Ruano, José L ^a   Pallarés, Antonio ^a,b   Vicioso, Mercedes ^a,b  

^a UNIVERSIDAD AUTÓNOMA DE MADRID   (Spain)

^b Deretil Research Institute   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

3,4 DIFLUOROANILINE; LEVOFLOXACIN; N (TERT BUTOXYCARBONYL) 3,4 DIFLUOROANILINE; OFLOXACIN; QUINOLINE DERIVED ANTIINFECTIVE AGENT; UNCLASSIFIED DRUG;

ANTIMICROBIAL ACTIVITY; ARTICLE; CHROMATOGRAPHY; DRUG POTENCY; DRUG SYNTHESIS; RACEMIC MIXTURE; STEREOCHEMISTRY;

EID: 0033166036     PISSN: 03855414     EISSN: None     Source Type: Journal    
DOI: 10.3987/com-99-8529     Document Type: Article

References (28)

1. a) M. P. Wentland, "The New Generation of Quinolones", ed. by C. Siporin, C. L. Heifetz, and J. M. Domagala, Marcel Dekker: New York, 1990.
2. b) D. T. W. Chu and P. B. Fernandes, Antimicrob. Agents Chemother., 1989, 33, 131.
3. V. T. Andriole, "The Quinolones", Academic Press, New York, 1988.
4. For some synthesis of ofloxacin or levofloxacin, see: a) S. B. Kang, E. J. Ahn, Y. Kim, and Y. H. Kim, Tetrahedron Lett., 1996, 37, 9317.
5. b) Daiichi Seiyaku, Drugs Future, 1992, 17, 559.
6. c) S. Atarashi, H. Tsurumi, T. Fujiwara, and I. Hayakawa, J. Heterocycl. Chem., 1991, 28, 329.
7. 3, 1989. (Chem. Abstr., 1989, 111, 134176z).
8. e) Daiichi Seiyaku, Eur. Pat. Appl. EP-206,283, 1986 (Chem. Abstr., 1987, 106, 119895t).
9. f) L. A. Mitscher, P. N. Sharma, D. T. W., Chu, L. L. Shen, and A. G. Pernet, J. Med. Chem., 1987, 30, 2283.
10. g) S. Atarashi, S. Yokohama, K. Yamazaki, M. Imamura, and I. Hayakawa, Chem. Pharm. Bull. Jpn., 1987, 35, 1896.
11. See also: h) K. Satoh, M. Inenaga, and K. Kanai, Tetrahedron: Asymmetry, 1998, 9, 2657.
12. i) A. Miyadera and A. Imura, Tetrahedron: Asymmetry, 1999, 10, 119.
13. j) Daiichi Seiyaku, Drugs Future, 1983, 8, 395.
14. J. C. Carretero, J. L. García Ruano, and M. Vicioso, Tetrahedron, 1992, 48, 7373.
15. For ortho-deprotonation of amides and carbamates of 3-fluoroaniline, see: a) R. D. Clark and A. M. Caroon, J. Org. Chem., 1982, 47, 2804.
16. For related processes, see: b) S. Takagishi, G. Katsoulos, and M. Schosser, Synlett, 1991, 360.
17. c) K. Smith and G. J. Pritchard, Angew. Chem., Int. Ed. Engl., 1990, 29, 282.
18. We have observed that 4 does not evolve into the benzyne (elimination of LiF) even after 2 h at 0 °C.
19. For related processes, see: a) J. M. Domagala, L. D. Hanna, C. L. Heifterz, P. M. Hutt, T. F. Mite, J. P. Sanchez, and M. Solomon, J. Med. Chem., 1986, 29, 394.
20. b) H. Egawa, J. Miyamoto, A. Minimida, Y. Nishimura, H. Okada, H. Uho, and J. Matsumoto, J. Med. Chem., 1984, 27, 1543.
21. For an example of synthesis of the quinolone skeleton by using the Gould-Jacobs sequence, see: I. Hayakawa, T. Hiramitsu, and Y. Tanaka, Chem. Pharm. Bull., 1984, 32, 4907. See also reference 3 and references cited therein.
22. 4 as Lewis acid in the nucleophilic opening of epoxides, see: M. Chini, P. Crotti, L. Favero, and M. Pineschi. Tetrahedron Lett., 1991, 32, 7583.
23. 2O) and further reaction with N-methylpiperazine (MeCN, 60 °C).
24. Likely in compound (10) the presence at C-7 of the highly electron-withdrawing sulfonyl group greatly activates the substitution of the fluorine atom at C-6. For a recent publication on regioselective substitutions in 6-fluoro-7-chloroquinolone acids, see: I. Hermecz, L. Vasvari-Debreczy, B. Podanyi, G. Kereszturi, M. Balogh, A. Horvath, and P. Varkonyi, Heterocycles, 1998, 48, 1111.
25. For the preparation of phenols by boration of aryllithiums and further oxidation, see for instance: a) M. Iwao, J. N. Reed, and V. Snieckus, J. Am. Chem. Soc., 1982, 104, 5531.
26. b) J. Green, J. Org. Chem., 1991, 56, 4325.
27. 1, 1994 (Chem. Abstr., 1994, 121, 9414n).
28. 2e[α]D=-76.9 °(c 0.65, NaOH).